Infectious cancer preserves dog genes for 11,000 years

The ancient tumour genes are most similar to modern huskies and Alaskan malamutes

(Image: Helen H. Richardson/Getty)

Call it the Methuselah mutt. There are genes from a dog that lived 11,000 years ago in an infectious cancer that forms tumours on the genitals of dogs today. The cancer genes therefore preserve information about early domesticated dogs.

Canine transmissible venereal tumour (CTVT) is one of only two known mammalian cancers that can move from animal to animal through physical contact. The other is a cancer transmitted between Tasmanian devils when they bite each other. A genetic analysis suggests that CTVT originated about 11,000 years ago, surviving the millennia by moving from dog to dog during mating.

“These tumours are in dogs all around the world, yet they all originate from one single dog that lived all those years ago,” says Elizabeth Murchison of the Wellcome Trust Sanger Institute in Hinxton, UK. Her team analysed DNA from two dogs with CTVT, one from Australia and one from Brazil.

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“It’s such a strange entity,” says Murchison. “It’s a cancer that’s become a parasite, and yet it came from the same species that is now its host.”

Cancer clones

Modern CTVT cells are clones of the original cancer, but over the millennia they have accumulated almost 2 million unique mutations through mistakes in cell duplication. By contrast, human tumours typically have just 1000 to 5000, says Murchison, because they are not transmissible so only live a few decades at most.

These mutations revealed CTVT’s age. By studying how many there were and working out the order and rate they appeared, the team calculated that the mother parasitic cell emerged 11,000 years ago. That is long after dogs first became domesticated, which may have happened as far back as 33,000 years ago.

“It’s intriguing how a tumour has survived for more than 10,000 years travelling round and infecting a very large number of dogs,” says Kerstin Lindblad-Toh of the Broad Institute in Cambridge, Massachusetts, head of the first team to sequence a dog’s genome in 2005. “If more examples [of transmissible cancers] were found, it would be interesting to see what genetic changes characterise this type of long-lived tumour.”

The samples taken from the Australian dog and the Brazilian dog seem to have diverged from one another about 500 years ago, at the height of European expansion. “It means that the cancer lived in just one small population of dogs for 10,500 years, but dogs carrying it were then picked up by explorers or seafarers who spread them, and the cancers they carried, all round the world,” says Murchison.

Apart from the mutations, the DNA in CTVT is identical to that of the dog in which it originated. By comparing the DNA in CTVT cells with DNA from modern dogs and wolves, Murchison pieced together what the first infected canine probably looked like.

“We put together a genetic identikit of the dog,” says Murchison. “It probably had a browny-grey agouti coat, a pointy snout, prickly ears, short hair, and was a dog, not a wolf,” she says. It was most similar to modern huskies and Alaskan malamutes, but its closest relatives may now be extinct.

Origin of cancer

Murchison says the cancer probably evolved in a badly inbred population, in which the cancer cells passed between the animals during sex, but were overlooked by the immune system because the dogs were so closely related.

CTVT is not an aggressive cancer and is easily curable in 90 per cent of cases, says Murchison. This may be because a mild form has evolved and adapted itself to life in its dog hosts. She adds that CTVT will probably go on for thousands more years, but may eventually go extinct if the cancer cells acquire too many mutations, which would cripple them.

No cancers of this kind have ever developed in people, but if they did, information from the Tasmanian devils and CTVT could help stop them, says Michael Stratton, also at the Wellcome Trust Sanger Institute.